p53 and HNSCC<NIH study..interesting, imho>
Abstract Number: 89
Presentation Title: Defective expression and function of p53 in head and neck squamous cell carcinoma cell lines
Presentation Start/End Time: Sunday, Apr 02, 2006, 8:00 AM -12:00 PM
Location: Exhibit Hall, Washington Convention Center
Poster Section: 4
Poster Board Number: 1
Author Block: Jay Friedman, Zhong Chen, Carter Van Waes. NIH-NIDCD, Bethesda, MD
TP53 is an important tumor suppressor gene that controls the cell cycle and apoptosis, and regulates the expression of many genes at the transcriptional level. p53 mutations have been observed in approximately 50% of head and neck squamous cell carcinoma (HNSCC), however, the molecular mechanisms of p53 have not been well understood for the cancers with either wild type or mutant p53. In this study, we investigated the expression pattern and function of wild type and mutant p53 in 9 human HNSCC cell lines (UM-SCC) and normal human keratinocytes. Among the 9 UM-SCC cells lines, 4 maintain wild type p53 status and 5 maintain mutant p53 status. cDNA microarray and real-time RT-PCR revealed a lower baseline level of p53 mRNA in cell lines with wild type p53 in comparison to normal keratinocytes. In contrast, there are comparable or higher baseline levels of p53 mRNA in mutant p53 cell lines in comparison to normal keratinocytes. Baseline levels of p53 protein were not detectable in wild type p53 cell lines by Western blot, however, there were higher baseline levels of mutant p53 protein detected in the mutant p53 cell lines when compared with normal keratinocytes. We further examined p53 expression and function under the treatment of cytotoxic agent doxorubicin (Dox). The exposure of normal keratinocytes to a 0.5µg/ml Dox increased p53 mRNA levels, p53 and p21 protein levels, and p53 binding activity. The p53 mRNA levels either remained unchanged or demonstrated a general decrease following Dox treatment in UM-SCC cell lines with either p53 status. No detectable p53 and p21 proteins, or p53 binding activity were observed in cell lines with wild type p53 after treatment. In cell lines with mutant p53, UM-SCC-11B and 38 showed increased levels of p53 and p21 protein, and p53 binding activity after Dox treatment. There was no change in p53 protein levels observed in cell lines 22A, 22B, and 46, and no change in p53 binding activity in 22A and 22B cells, however, cell line 46 showed a decrease in p53 binding activity. p21 protein levels increased in cell lines 22A, 22B, and 46 following Dox treatment. Our data suggest that the defective expression and function of both wild type and mutant p53 could be an important tumorigeneic mechanism in HNSCC cells. The aberrant p53 mRNA expression could contribute to such mechanisms in addition to the regulation at the level of protein degradation and interaction. Research was supported by the Intramural Research Program, NIDCD, project DC-00016 |
